CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis

Jian-Wei Hao, Juan Wang, Huiling Guo, Yin-Yue Zhao, Hui-Hui Sun, Yi-Fan Li, Xiao-Ying Lai, Ning Zhao, Xu Wang, Changchuan Xie, Lixin Hong, Xi Huang, Hong-Rui Wang, Cheng-Bin Li, Bin Liang, Shuai Chen () and Tong-Jin Zhao ()
Additional contact information
Jian-Wei Hao: Xiamen University
Juan Wang: Xiamen University
Huiling Guo: Xiamen University
Yin-Yue Zhao: Xiamen University
Hui-Hui Sun: Xiamen University
Yi-Fan Li: Xiamen University
Xiao-Ying Lai: Xiamen University
Ning Zhao: Xiamen University
Xu Wang: Fudan University
Changchuan Xie: Xiamen University
Lixin Hong: Xiamen University
Xi Huang: Xiamen University
Hong-Rui Wang: Xiamen University
Cheng-Bin Li: Yunnan University
Bin Liang: Yunnan University
Shuai Chen: Nanjing University
Tong-Jin Zhao: Xiamen University

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.

Date: 2020
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DOI: 10.1038/s41467-020-18565-8

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